Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study
Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino-acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic st...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Oxford University Press
2021
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| _version_ | 1797106354982223872 |
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| author | Aglago, EK Schalkwijk, CG Freisling, H Fedirko, V Hughes, DJ Jiao, L Dahm, CC Olsen, A Tjønneland, A Katzke, V Johnson, T Schulze, MB Aleksandrova, K Masala, G Sieri, S Simeon, V Tumino, R Macciotta, A Bueno-de-Mesquita, B Skeie, G Gram, IT Sandanger, T Jakszyn, P Sánchez, M-J Amiano, P Colorado-Yohar, SM Gurrea, AB Mayén, A-L Weiderpass, E Gunter, MJ Heath, AK Jenab, M |
| author_facet | Aglago, EK Schalkwijk, CG Freisling, H Fedirko, V Hughes, DJ Jiao, L Dahm, CC Olsen, A Tjønneland, A Katzke, V Johnson, T Schulze, MB Aleksandrova, K Masala, G Sieri, S Simeon, V Tumino, R Macciotta, A Bueno-de-Mesquita, B Skeie, G Gram, IT Sandanger, T Jakszyn, P Sánchez, M-J Amiano, P Colorado-Yohar, SM Gurrea, AB Mayén, A-L Weiderpass, E Gunter, MJ Heath, AK Jenab, M |
| author_sort | Aglago, EK |
| collection | OXFORD |
| description | Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino-acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic studies are inconclusive. We conducted a case-control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs: N ε-(carboxy-methyl)lysine (CML), N ε-(carboxy-ethyl)lysine (CEL) and N δ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured by ultra-performance liquid chromatography tandem mass-spectrometry in baseline samples collected from 1,378 incident primary colorectal cancer cases and 1,378 matched controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression for colorectal cancer risk associated with CML, CEL, MG-H1, total AGEs, and [CEL+MG-H1: CML] and [CEL:MG-H1] ratios. Inverse colorectal cancer risk associations were observed for CML (OR comparing highest to lowest quintile, ORQ5vs.Q1=0.40, 95%CI:0.27-0.59), MG-H1 (ORQ5vs.Q1=0.73, 95%CI:0.53 - 1.00) and total AGEs (OR Q5vs.Q1=0.52, 95%CI:0.37 - 0.73) whereas no association was observed for CEL. A higher [CEL+MG-H1: CML] ratio was associated with colorectal cancer risk (ORQ5vs.Q1=1.91, 95%CI:1.31-2.79). The associations observed did not differ by sex, or by tumour anatomical subsite. Although individual AGEs concentrations appear to be inversely associated with colorectal cancer risk, a higher ratio of methylglyoxal-derived AGEs versus those derived from glyoxal (calculated by [CEL+MG-H1: CML] ratio) showed a strong positive risk association. Further insight on the metabolism of AGEs and their dicarbonyls precursors, and their roles in colorectal cancer development is needed. |
| first_indexed | 2024-03-07T07:01:49Z |
| format | Journal article |
| id | oxford-uuid:e82cba22-eda3-4fd2-973d-dcb7b7ee158d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:01:49Z |
| publishDate | 2021 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:e82cba22-eda3-4fd2-973d-dcb7b7ee158d2022-03-29T07:52:06ZPlasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e82cba22-eda3-4fd2-973d-dcb7b7ee158dEnglishSymplectic ElementsOxford University Press2021Aglago, EKSchalkwijk, CGFreisling, HFedirko, VHughes, DJJiao, LDahm, CCOlsen, ATjønneland, AKatzke, VJohnson, TSchulze, MBAleksandrova, KMasala, GSieri, SSimeon, VTumino, RMacciotta, ABueno-de-Mesquita, BSkeie, GGram, ITSandanger, TJakszyn, PSánchez, M-JAmiano, PColorado-Yohar, SMGurrea, ABMayén, A-LWeiderpass, EGunter, MJHeath, AKJenab, MAdvanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino-acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic studies are inconclusive. We conducted a case-control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs: N ε-(carboxy-methyl)lysine (CML), N ε-(carboxy-ethyl)lysine (CEL) and N δ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured by ultra-performance liquid chromatography tandem mass-spectrometry in baseline samples collected from 1,378 incident primary colorectal cancer cases and 1,378 matched controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression for colorectal cancer risk associated with CML, CEL, MG-H1, total AGEs, and [CEL+MG-H1: CML] and [CEL:MG-H1] ratios. Inverse colorectal cancer risk associations were observed for CML (OR comparing highest to lowest quintile, ORQ5vs.Q1=0.40, 95%CI:0.27-0.59), MG-H1 (ORQ5vs.Q1=0.73, 95%CI:0.53 - 1.00) and total AGEs (OR Q5vs.Q1=0.52, 95%CI:0.37 - 0.73) whereas no association was observed for CEL. A higher [CEL+MG-H1: CML] ratio was associated with colorectal cancer risk (ORQ5vs.Q1=1.91, 95%CI:1.31-2.79). The associations observed did not differ by sex, or by tumour anatomical subsite. Although individual AGEs concentrations appear to be inversely associated with colorectal cancer risk, a higher ratio of methylglyoxal-derived AGEs versus those derived from glyoxal (calculated by [CEL+MG-H1: CML] ratio) showed a strong positive risk association. Further insight on the metabolism of AGEs and their dicarbonyls precursors, and their roles in colorectal cancer development is needed. |
| spellingShingle | Aglago, EK Schalkwijk, CG Freisling, H Fedirko, V Hughes, DJ Jiao, L Dahm, CC Olsen, A Tjønneland, A Katzke, V Johnson, T Schulze, MB Aleksandrova, K Masala, G Sieri, S Simeon, V Tumino, R Macciotta, A Bueno-de-Mesquita, B Skeie, G Gram, IT Sandanger, T Jakszyn, P Sánchez, M-J Amiano, P Colorado-Yohar, SM Gurrea, AB Mayén, A-L Weiderpass, E Gunter, MJ Heath, AK Jenab, M Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study |
| title | Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study |
| title_full | Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study |
| title_fullStr | Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study |
| title_full_unstemmed | Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study |
| title_short | Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study |
| title_sort | plasma concentrations of advanced glycation end products and colorectal cancer risk in the epic study |
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